Variant 4-110476522-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000265162.10(ENPEP):c.108C>T(p.Ala36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,603,474 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 190 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 181 hom. )

Consequence

ENPEP
ENST00000265162.10 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.94

Variant links:

Genes affected

ENPEP (HGNC:3355): (glutamyl aminopeptidase) The ENPEP gene encodes glutamyl aminopeptidase, a type II integral membrane protein with an extracellular zinc-binding domain. This protein can upregulate blood pressure by cleaving the N-terminal aspartate from angiotensin II, and can regulate blood vessel formation and enhance tumorigenesis in some tissues. Along with ANPEP and DPP4, ENPEP was found to be a candidate co-receptor for the coronavirus SARS-CoV-2, which causes COVID-19. [provided by RefSeq, Apr 2020]

ENPEP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 4-110476522-C-T is Benign according to our data. Variant chr4-110476522-C-T is described in ClinVar as [Benign]. Clinvar id is 780491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPEP	NM_001977.4 linkuse as main transcript	c.108C>T	p.Ala36=	synonymous_variant	1/20	ENST00000265162.10	NP_001968.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPEP	ENST00000265162.10 linkuse as main transcript	c.108C>T	p.Ala36=	synonymous_variant	1/20	1	NM_001977.4	ENSP00000265162	P1
ENPEP	ENST00000510961.1 linkuse as main transcript	n.73-12019C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0264

AC:

4014

AN:

152100

Hom.:

189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0915

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00695

AC:

1706

AN:

245502

Hom.:

AF XY:

0.00528

AC XY:

699

AN XY:

132330

show subpopulations

Gnomad AFR exome

AF:

0.0913

Gnomad AMR exome

AF:

0.00476

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000306

Gnomad OTH exome

AF:

0.00402

GnomAD4 exome

AF:

0.00286

AC:

4146

AN:

1451256

Hom.:

181

Cov.:

AF XY:

0.00251

AC XY:

1811

AN XY:

720208

show subpopulations

Gnomad4 AFR exome

AF:

0.0973

Gnomad4 AMR exome

AF:

0.00519

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000153

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000232

Gnomad4 OTH exome

AF:

0.00602

GnomAD4 genome

AF:

0.0264

AC:

4024

AN:

152218

Hom.:

190

Cov.:

AF XY:

0.0263

AC XY:

1961

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0916

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0136

Hom.:

Bravo

AF:

0.0303

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.61

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over